Increased lung vascular permeability is a hallmark of acute respiratory distress syndrome (ARDS). It has been established that endothelium regulates passage of plasma proteins and other macromolecules across the vessel wall and performs the vital task of maintaining the integrity of the alveolar-capillary barrier. See Mehta and Malik, Physiol. Rev., January 2006; 86(1):279-367. Endothelial cells regulate the barrier properties of the microvessel wall by altering their shape, which was earlier described as “cell rounding” by Majno and Palade (1961). See Majno et al., J. Biophys. Biochem. Cytol., December, 1961: 11:571-605. Cell shape change occurs as a result of actinomyosin-based endothelial cell contraction, requiring myosin light chain (MLC) phosphorylation. See Mehta and Malik, Physiol. Rev., January 2006; 86(1):279-367. The phosphorylation of MLC is catalyzed by activated myosin light chain kinase (MLCK) in the presence of ionized intracellular calcium and calmodulin.3 Several studies using either constitutively active MLCK or pharmacological inhibitors of MLCK have shown that MLCK-induced MLC phosphorylation plays an essential role in regulating endothelial permeability in vitro and in vivo.3-10 In addition, studies indicate that increased MLCK activity and MLC phosphorylation in endothelial cell monolayers are required for transendothelial polymorphonuclear (“PMN”) migration elicited by chemotactic agents.11, 12 Importantly, recent gene expression profiling studies from several acute lung injury patients have identified SNPs (single-nucleotide polymorphisms) in the MLCK gene (MYLK) that may be associated with ARDS. MLCK is thus indicated to be a potential therapeutic target for treating ARDS.13, 14 
Interestingly, primary endothelial cells are known to express the 210 kDa long isoform of MLCK referred to as endothelial MLCK-L and the well-known 130 kDa smooth muscle MLCK isoform (MLCK-S, as used herein).9, 15-17 These isoforms are encoded from a single gene on chromosome 3. Structurally, MLCK-L contains all the domains present in the smooth muscle isoform, but in addition, has a unique 922-amino acid N-terminal domain containing consensus sites for phosphorylation by multiple protein kinases, including cAMP-dependent protein kinase A (PKA), PKC, PAK, Src, and Ca2+/CaM-dependent protein kinase II.1, 3. The N-terminus of MLCK-L has been shown to interact with Src.3 Macrophage inhibitory factor18 and microtubules19 also bind with high affinity to the N-terminus of MLCK-L. Thus, regulation of MLCK-L by serine and tyrosine kinases, and its complexation with multiple proteins indicate that many signaling pathways may exert control on endothelial permeability by converging to MLCK-L. However, previous studies using approaches which target the kinase activity of MLCK without isoform specificity have not been clear in identifying the individual role of MLCK-L in regulating endothelial barrier function. In accordance with various aspects and embodiments of the invention herein disclosed an siRNA sequence that specifically “knocks down” MLCK-L in cultured cells was developed and used in a recently developed strain of mice lacking MLCK-L (MLCK210−/− mice)6 to show the importance of MLCK210 in the mechanism of increased lung vascular permeability. A thrombin or a PAR-1 peptide agonist was used to elicit an endothelial permeability response because PAR-1 receptor agonists are known to increase endothelial permeability by actinomyosin induced contraction downstream of G-protein-coupled proteinase-activated receptor-1 (PAR-1) in endothelial monolayer as well as in vivo models.1 The results show that, in accordance with the invention. MLCK-L is a key effector mediating the PAR-1-induced increase in lung vascular permeability in part through phosphorylation of MLC and MLCK is involved in regulation of calcium entry via a previously undescribed interaction with store operated channels.